Leukotrienes structure proof

Natural products Before the advent of spectroscopic methods (UV, IR, NMR, MS), total synthesis by independent methods was a way to achieve a proof of the proposed structure of a molecule. Today, spectroscopic methods solve most structural problems. Total synthesis by independent routes is still used occasionally as structural proofs, and recent examples are provided by Corey [5] in the synthesis of leukotriene and Kishi [6] in the synthesis of palytoxine. Today, most natural product synthesis is used to prepare sufficient amounts of interesting compounds, e.g. 

Despite these uncertainties, several groups set out to prepare the proposed leukotriene structures, and during these syntheses some interesting observations were made with respect to the double-bond stereochemistry which eventually lead to modification of the proposed structures for LTA4 and LTC4. These observations are outlined here in a historical context to indicate their contribution to the final structure proof of the leukotrienes. 

During the course of synthesis and structure proof of the leukotrienes, it was important to synthesize the four optical isomers derivable from the two asymmetric centers at C-5 and C-6 of the eicosatetraeonic acid chain in order to fully confirm that the natural compounds had the (5S,6/ ) configuration. It was also of considerable scientific interest to find out what effect changes in configuration on these centers would have upon the biological activity of the compounds. 

As part of their work in the structure proof of the natural leukotrienes, Corey s group carried out a stereospecific synthesis of 6-epi-LTA4 methyl ester as discussed earlier (Scheme 3.29). Coupling of the epoxide with the appropriately... 

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